[Incapacity to work in prehospital German emergency medical services staff]. / Arbeitsunfähigkeit bei präklinischen Rettungskräften in Deutschland: Ergebnisse der EMS-Health-Studie.

Background: The determination of incapacity to work is a central approach for analyses of absence due to sickness. Nevertheless, no data are yet available for incapacity to work and associated factors in the German prehospital emergency medical services (EMS) staff. Objective: The aim of this analysis was to identify the proportion of EMS staff with at least one incapacity for work (AU) in the previous 12 months and associated factors. Material and methods: This was a nationwide survey study with rescue workers. Factors associated with work disability were identified using multivariable logistic regression, calculating odds ratios (OR) and associated 95% confidence intervals (95% CI). Results: Included in this analysis were 2298 employees of the German emergency medical services (female 42.6%, male 57.2%). Overall, 60.10% of female participants and 58.98% of male participants reported an incapacity for work in the previous 12 months. Incapacity for work was significantly associated with having a high school diploma (high school diploma: OR: 0.51, 95% CI 0.30; 0.88, p = 0.016; reference: secondary school diploma), working in a rural environment (OR: 0.65, 95% CI 0.50; 0.86, p = 0.003) or urban environment (OR: 0.72, 95% CI: 0.53; 0.98, p = 0.037). Furthermore, hours worked per week (OR: 1.01, 95% CI: 1.00; 1.02, p = 0.003) and 5-< 10 years of service (OR: 1.40, 95% CI: 1.04; 1.89, p = 0.025) were associated with higher odds of work disability. Neck and back pain, depression, osteoarthritis, and asthma in the previous 12 months also showed a significant association with work disability in the same time period. Conclusion: This analysis shows that chronic diseases, educational attainment, area of assignment, years of service, and hours worked per week, among others, were associated with incapacity for work in the previous 12 months in German EMS staff.

Prevalence of pain, analgesic self-medication and mental health in German pre-hospital emergency medical service personnel: a nationwide survey pilot-study.

PURPOSE: The aim of this study was to estimate the prevalence of pain, the extent of analgesics intake and the mental health status of German pre-hospital emergency medical service (EMS) personnel. METHODS: We conducted a nationwide online survey, which consisted of sociodemographic and job-related items, questions on pain and analgesics intake and the short-version of the validated Depression-Anxiety-Stress Scale (DASS-21). RESULTS: A total of 774 EMS personnel with a mean age of 33.03 (standard error [SE] 0.37) years were included into the final analysis of which 23.77% were female. Pain was reported by 58.64% (454 of 774) of the study participants with 10.72% (95% confidence interval [CI] 8.54%; 13.29%) suffering from chronic, 1.68% (95% CI 0.89%; 2.87%) from acute and 46.25% (95% CI 41.49%; 51.30%) from recurrent pain, respectively. Most frequent location of pain was lumbar spine. Analgesics were used by 52.76% (239 of 454) of pre-hospital EMS personnel with pain (acute 76.92% / chronic 69.88% / recurrent 47.90%). Moreover, participants with chronic and recurrent pain indicated significantly higher depression (p ≤ 0.001), anxiety (p ≤ 0.001), and stress (p ≤ 0.001) levels compared to those without pain, respectively. CONCLUSION: This study indicates a high prevalence of pain and analgesics usage in participating German pre-hospital EMS personnel and a poorer mental health in those with chronic and recurrent pain. Therefore, disease prevention and health promotion measures are needed to preserve health of pre-hospital EMS personnel.

Risk of falls in postmenopausal women treated with romosozumab: Preliminary indices from a meta-analysis of randomized, controlled trials.

OBJECTIVES: Falls are the well-known risk factor for osteoporotic fractures and some medications can increase the risk of falls. Therefore, the aim of our study is to evaluate the effect of romosozumab on risk of falls in postmenopausal women. METHODS: Studies were searched on PubMed, Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov using the search term "romosozumab." Randomized, clinical trials with romosozumab in postmenopausal women, which met the inclusion criteria and in particular reported on falls in safety or efficacy data, were included into the meta-analysis. Risk ratios (RRs) and corresponding 95% confidence intervals (CIs) were calculated using a binary effects model. RESULTS: A total of four studies with overall 12,128 postmenopausal women with osteoporosis were included into the meta-analysis. Twelve-months treatment with romosozumab reduced the risk of falls nonsignificantly by 16% (RR, 0.84; 95% CI, 0.67-1.04; P = 0.10; n = 11,829). A subgroup analysis with double-blind studies indicated a statistically significant reduction in risk of falls by 20% (RR, 0.80; 95% CI, 0.71-0.92; P ≤ 0.01; n = 11,211). A sequential treatment of romosozumab followed by an antiresorptive medication resulted in a 12% (RR, 0.88; 95% CI, 0.80-0.96; P ≤ 0.01; n = 11,211) reduction of falls in the romosozumab group compared to the control group. CONCLUSIONS: This analysis indicates that romosozumab has a tendency to reduce risk of falls in postmenopausal women with osteoporosis. Nevertheless, our findings are preliminary results with a low significance and to confirm these findings more data and analyses are needed.

Solution structure of the autophagy-related protein LC3C reveals a polyproline II motif on a mobile tether with phosphorylation site.

(Macro-)autophagy is a compartmental degradation pathway conserved from yeast to mammals. The yeast protein Atg8 mediates membrane tethering/hemifusion and cargo recruitment and is essential for autophagy. The human MAP1LC3/GABARAP family proteins show high sequence identity with Atg8, but MAP1LC3C is distinguished by a conspicuous amino-terminal extension with unknown functional significance. We have determined the high-resolution three-dimensional structure and measured the backbone dynamics of MAP1LC3C by NMR spectroscopy. From Ser18 to Ala120, MAP1LC3C forms an α-helix followed by the ubiquitin-like tertiary fold with two hydrophobic binding pockets used by MAP1LC3/GABARAP proteins to recognize targets presenting LC3-interacting regions (LIRs). Unlike other MAP1LC3/GABARAP proteins, the amino-terminal region of MAP1LC3C does not form a stable helix α1 but a "sticky arm" consisting of a polyproline II motif on a flexible linker. Ser18 at the interface between this linker and the structural core can be phosphorylated in vitro by protein kinase A, which causes additional conformational heterogeneity as monitored by NMR spectroscopy and molecular dynamics simulations, including changes in the LIR-binding interface. Based on these results we propose that the amino-terminal polyproline II motif mediates specific interactions with the microtubule cytoskeleton and that Ser18 phosphorylation modulates the interplay of MAP1LC3C with its various target proteins.

Integrated NMR, Fluorescence, and Molecular Dynamics Benchmark Study of Protein Mechanics and Hydrodynamics.

Understanding the function of a protein requires not only knowledge of its tertiary structure but also an understanding of its conformational dynamics. Nuclear magnetic resonance (NMR) spectroscopy, polarization-resolved fluorescence spectroscopy and molecular dynamics (MD) simulations are powerful methods to provide detailed insight into protein dynamics on multiple time scales by monitoring global rotational diffusion and local flexibility (order parameters) that are sensitive to inter- and intramolecular interactions, respectively. We present an integrated approach where data from these techniques are analyzed and interpreted within a joint theoretical description of depolarization and diffusion, demonstrating their conceptual similarities. This integrated approach is then applied to the autophagy-related protein GABARAP in its cytosolic form, elucidating its dynamics on the pico- to nanosecond time scale and its rotational and translational diffusion for protein concentrations spanning 9 orders of magnitude. We compare the dynamics of GABARAP as monitored by 15N spin relaxation of the backbone amide groups, fluorescence anisotropy decays and fluorescence correlation spectroscopy of side chains labeled with BODIPY FL, and molecular movies of the protein from MD simulations. The recovered parameters agree very well between the distinct techniques if the different measurement conditions (probe localization, sample concentration) are taken into account. Moreover, we propose a method that compares the order parameters of the backbone and side chains to identify potential hinges for large-scale, functionally relevant intradomain motions, such as residues 27/28 at the interface between the two subdomains of GABARAP. In conclusion, the integrated concept of cross-fertilizing techniques presented here is fundamental to obtaining a comprehensive quantitative picture of multiscale protein dynamics and solvation. The possibility to employ these validated techniques under cellular conditions and combine them with fluorescence imaging opens up the perspective of studying the functional dynamics of GABARAP or other proteins in live cells.